The direct binding of a p58 killer cell inhibitory receptor to human histocompatibility leukocyte antigen (HLA)-Cw4 exhibits peptide selectivity.
The direct binding of a p58 killer cell inhibitory receptor to human histocompatibility leukocyte antigen (HLA)-Cw4 exhibits peptide selectivity.
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DOI：
10.1084/jem.185.8.1523
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发表时间：
1997-04-21
期刊：
影响因子：
--
通讯作者：
Long EO
中科院分区：
文献类型：
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作者：
Rajagopalan S;Long EO
小鼠和人类的自然杀伤细胞（NK）表达许多结构多样的受体，当识别靶细胞上表达的主要组织相容性复合体（MHC） I类分子时，这些受体抑制靶细胞裂解。肽对NK细胞抑制所需的I类结构特征的贡献似乎因受体的类型而异。因此，在小鼠中，虽然Ly-49A介导的NK抑制没有肽特异性，但人类组织相容性抗原(HLA)-B*2705特异性NK克隆对肽具有选择性。在本报告中，我们研究了肽在定义的杀伤细胞抑制受体（KIR） cl42识别HLA-C中的作用，并确定了对HLA-Cw4的特异性。可溶性KIR cl42分子与抗原呈递相关转运体（TAP）缺陷的RMA-S细胞上表达的HLA-Cw4的结合仅在外源肽加载时发生。此外，尽管HLA-C的表面表达相似，但非单体肽QYDDAVYKL的7和8位的某些取代消除了Cw4与KIR cl42的相互作用，这也存在肽选择性。RMA-S细胞上携带肽的HLA-Cw4与可溶性KIR cl42之间的这种直接相互作用的特异性与NK克隆的识别相关，因为它们仅被携带适当肽的HLA-Cw4抑制。
Natural killer (NK) cells in mice and humans express a number of structurally diverse receptors that inhibit target cell lysis upon recognition of major histocompatibility complex (MHC) class I molecules expressed on targets. The contribution of peptide to the structural features of class I required for NK cell inhibition appears to vary depending on the type of receptor engaged. Thus, while there is no peptide specificity in NK inhibition mediated by Ly-49A in the mouse, human histocompatibility antigen (HLA)-B*2705–specific NK clones displayed selectivity for peptides. In this report, we examine the role of peptide in the recognition of HLA-C by the defined killer cell inhibitory receptor (KIR) cl42 with established specificity for HLA-Cw4. Binding of soluble KIR cl42 molecules to HLA-Cw4 expressed on transporter associated with antigen presentation (TAP)-deficient RMA-S cells occurred only upon exogenous peptide loading. Moreover, there was peptide selectivity in that certain substitutions at positions 7 and 8 of the nonamer peptide QYDDAVYKL abolished Cw4 interaction with KIR cl42 despite similar surface expression of HLA-C. The specificity of this direct interaction between peptideloaded HLA-Cw4 on RMA-S cells and soluble KIR cl42 correlated with recognition by NK clones in that they were inhibited only by HLA-Cw4 loaded with the appropriate peptides.